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1.
BMC Cardiovasc Disord ; 20(1): 145, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32204696

RESUMO

BACKGROUND: We hypothesized that discriminating the early subclinical organ damage would serve as a great opportunity for prevention against atherosclerotic cardiovascular disease (ASCVD). Brachial-ankle pulse wave velocity (baPWV), low retinal vascular fractal dimension, and albuminuria are surrogates of subclinical vascular changes. METHODS: The aim of this study was to use Pooled Cohort Equations (PCE) and ASCVD risk equations derived from "Prediction for ASCVD Risk in China project (CHINA-PAR)" to observe the prevalence of macro- and microcirculation abnormalities. A total of 2166 subjects were involved. Characteristics were investigated using questionnaire and physical examinations. We calculated the urine albumin to creatinine ratio (UACR). The baPWV was measured using a fully automatic arteriosclerosis detector. The retinal vascular fractal dimension was measured by a semiautomated computer-based program. The 10-year ASCVD risk was estimated using the PCE and CHINA-PAR model. RESULTS: The cut-off values for the elevated baPWV were 2.82 and 2.92% in the PCE model and CHINA-PAR model, respectively, with nearly 85% sensitivity and an average specificity of 74%. For low retinal fractal dimension, at the cut-off point of 3.8%, we acquired an acceptable sensitivity of 66.27-68.24% and specificity of 62.57-67.45%. All the C-statistics presented a significant improvement from the PCE model to the CHINA-PAR model (P < 0.05). For all categories-net reclassification improvement (NRI) values were significant and clearly varied (0.329, 0.183, and 0.104, respectively) depending on the cut-off set at 3%. CONCLUSION: Our study demonstrated that the CHINA-PAR equations rather than PCE could provide better identification of macro- and microcirculation abnormalities. A lower cut-off point for the subclinical vascular changes may be selected in a population from southeast China.

2.
BMC Nephrol ; 21(1): 90, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156263

RESUMO

BACKGROUND: DD was found to be associated with acute myocardial infarction (AMI) and renal insufficiency. However, it is uncertain whether DD is an independent risk factor of CI-AKI in patients undergoing pPCI. METHODS: We prospectively enrolled 550 consecutive patients with STEMI undergoing pPCI between January 2012 and December 2016. The predictive value of admission DD for CI-AKI was assessed by receiver operating characteristic (ROC) and multivariable logistic regression analysis. CI-AKI was defined as an absolute serum creatinine increase ≥0.3 mg/dl or a relative increase in serum creatinine ≥50% within 48 h of contrast medium exposure. RESULTS: Overall, the incidence of CI-AKI was 13.1%. The ROC analysis showed that the cutoff point of DD was 0.69 µg/ml for predicting CI-AKI with a sensitivity of 77.8% and a specificity of 57.3%. The predictive value of DD was similar to the Mehran score for CI-AKI (AUCDD = 0.729 vs AUCMehran = 0.722; p = 0.8298). Multivariate logistic regression analysis indicated that DD > 0.69 µg/ml was an independent predictor of CI-AKI (odds ratio [OR] = 3.37,95% CI:1.80-6.33, p < 0.0001). Furthermore, DD > 0.69 µg/ml was associated with an increased risk of long-term mortality during a mean follow-up period of 16 months (hazard ratio = 3.41, 95%CI:1.4-8.03, p = 0.005). CONCLUSION: Admission DD > 0.69 µg/ml was a significant and independent predictor of CI-AKI and long-term mortality in patients undergoing pPCI.

3.
Int J Mol Med ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32186749

RESUMO

Sonic hedgehog (Shh) is pivotally important in embryonic and adult blood vessel development and homeostasis. However, whether Shh is involved in atherosclerosis and plays a role in endothelial apoptosis induced by oxidized low­density lipoprotein (ox­LDL) has not been reported. The present study used recombinant Shh­N protein (rShh­N) and a plasmid encoding the human Shh gene (phShh) to investigate the role of Shh in ox­LDL­mediated human umbilical vein endothelial cell (HUVEC) apoptosis. The present study found that ox­LDL was able to induce apoptosis in HUVECs and that Shh protein expression was downregulated. Furthermore, pretreatment with rShh­N or transfection with phShh increased anti­apoptosis protein Bcl­2 expression and decreased cell apoptosis. These protective effects of rShh­N could be abolished by cyclopamine, which is a hedgehog signaling inhibitor. Furthermore, a co­immunoprecipitation assay was performed to demonstrate that Shh interacted with NF­κB p65 in HUVECs. Additionally, ox­LDL upregulated the phosphorylation of NF­κB p65 and inhibitor of NF­κB­α (IκBα), and these effects decreased notably following rShh­N and phShh treatment. Together, the present findings suggested that Shh serves an important protective role in alleviating ox­LDL­mediated endothelial apoptosis by inhibiting the NF­κB signaling pathway phosphorylation and Bcl­2 mediated mitochondrial signaling.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32113679

RESUMO

Endothelial inflammation is an important contributor to the pathology of atherosclerotic cardiovascular disease (ASCVD). Circular RNAs (circRNAs) function and role in endothelium inflammation still unknown. In our present study, we firstly identified that circ-RELL1 plays a proinflammatory role in ox-LDL-induced HUVECs through high-throughput circRNA microarray assays. Knockdown circ-RELL1 can reduce the expression of ICAM1 and VCAM1 in ox-LDL induced endothelium inflammation. Mechanistically, circ-RELL1 directly bound to miR-6873-3p in cytoplasm. Subsequently miR-6873-3p reduced MyD88 (myeloid differentiation primary response 88) protein expression and alleviated MyD88 medicated NF-κB activation. Furthermore, circ-RELL1 can abolish the inhibition of inflammation response by miR-6873-3p. Our findings illustrate a novel regulatory pathway that circ-RELL1 modulate inflammatory response by miR-6873-3p/MyD88/NF-κB axis in ox-LDL induced endothelial cells, which provides a potential therapeutic candidate for endothelium inflammation in atherosclerotic cardiovascular disease.

5.
Neuroscience ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31982470

RESUMO

OBJECTIVE: The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells. METHODS: at SAN cells were isolated by trypsinization and identified based on morphology and electrophysiology. If and HCN currents were recorded via patch clamp technique. The expression of the HCN channel protein was determined by Western blotting analysis. RESULTS: The diastolic depolarization rate of spontaneous action potentials and the current densities of If were reduced by exposure to 10 µM CPA. The inhibitory effect of CPA was concentration-dependent with an IC50 value of 16.3 µM and a Hill coefficient of 0.98. The effect of CPA on If current was also time-dependent, and the If current amplitude was partially restored after washout. Furthermore, the steady-state activation curve of the If current was shifted to a negative potential, indicating that channel activation slowed down. Finally, the protein expression of HCN4 in HEK293 cells was markedly downregulated by CPA. CONCLUSIONS: These results indicate that the direct inhibition effect of CPA on the If current in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.

6.
J Cell Physiol ; 235(1): 317-327, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31215035

RESUMO

Cardiomyocyte function and viability are highly modulated by mammalian Ste20-like kinase 1 (Mst1)-Hippo pathway and mitochondria. Mitophagy, a kind of mitochondrial autophagy, is a protective program to attenuate mitochondrial damage. However, the relationship between Mst1 and mitophagy in septic cardiomyopathy has not been explored. In the present study, Mst1 knockout mice were used in a lipopolysaccharide (LPS)-induced septic cardiomyopathy model. Mitophagy activity was measured via immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay. Pathway blocker and small interfering RNA were used to perform the loss-of-function assay. The results demonstrated that Mst1 was rapidly increased in response to LPS stress. Knockout of Mst1 attenuated LPS-mediated inflammation damage, reduced cardiomyocyte death, and improved cardiac function. At the molecular levels, LPS treatment activated mitochondrial damage, such as mitochondrial respiratory dysfunction, mitochondrial potential reduction, mitochondrial ATP depletion, and caspase family activation. Interestingly, in response to mitochondrial damage, Mst1 deletion activated mitophagy which attenuated LPS-mediated mitochondrial damage. However, inhibition of mitophagy via inhibiting parkin mitophagy abolished the protective influences of Mst1 deletion on mitochondrial homeostasis and cardiomyocyte viability. Overall, our results demonstrated that septic cardiomyopathy is linked to Mst1 upregulation which is followed by a drop in the protective mitophagy.

7.
Med Sci Monit ; 25: 9290-9298, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31806860

RESUMO

BACKGROUND Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis. MATERIAL AND METHODS A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins. RESULTS The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-kappaB, IL-6, IL-1ß, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P<0.05). Compared with the LPS group, the expression of NF-kappaB, TNF-alpha, IL-6, IL-1ß, and TLR4 in the LPS+resveratrol group was decreased. The expression of p-PI3K, p-AKT, and p-mTOR in LPS+LY294002 was reduced. The expression p-PI3K, p-AKT, and p-mTOR in the myocardium of the LPS+resveratrol group was increased. CONCLUSIONS Resveratrol can protect the myocardium in sepsis by activating the PI3K/AKT/mTOR signaling pathway and inhibiting the NF-kappaB signaling pathway and related inflammatory factors.

8.
Med Sci Monit ; 25: 9973-9980, 2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31875645

RESUMO

BACKGROUND As epidemiological findings are still controversial, animal experiments have probed into the potential link between uric acid and damage to microvessels. The present study examined the association of serum uric acid (SUA) with the retinal vascular caliber and retinal vascular fractal dimension (Df) in males and females utilizing a cross-sectional study design. MATERIAL AND METHODS A total of 2169 subjects from 7 sampling units were enrolled. Retinal vascular parameters were analyzed with a semi-automated computer-based program. The central retinal arteriolar equivalent, central retinal venular equivalent, and Df were linearly and categorically measured in males and females and at various SUA levels. RESULTS The analysis revealed that per SD SUA increase was associated with an increase of 0.848 µm in the arteriolar caliber, and an increase of 1.618 µm in the venular caliber only in females. No significant correlation was found between Df and SUA in females or in males. Further adjusted for more cardiovascular risk factors did not change the results. CONCLUSIONS By exploring a Chinese coastal population, we elucidate the association between SUA with retinal arterioles and venules in females. Df, as a mathematical index of retinal blood vascular complexity, is not correlated with SUA or hyperuricemia.

10.
J Atheroscler Thromb ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31406054

RESUMO

AIM: Our study investigated the association between soluble endoglin and carotid subclinical atherosclerosis. METHODS: We used endoglin as an adjunct to atherosclerotic cardiovascular disease (ASCVD) risk, in recognition of carotid clinical atherosclerosis, in order to explore a new model to refine risk assessment. Out of 3,452 participants, 978 subjects with detected soluble endoglin were enrolled in a cross-sectional investigation in Fujian Province were enrolled. Soluble endoglin concentration in serum samples was evaluated using an enzyme-linked immunosorbent assay method. Carotid ultrasonography was used to detect intima-media thickness and carotid plaque. RESULTS: The mean 10-year ASCVD risk by the new Pooled Cohort Equations accounted for 10.04% (±12.35). The mean soluble endoglin level was 15.35 ng/ml (±6.64). Multivariable regression demonstrated that age, systolic blood pressure, diastolic blood pressure, total cholesterol, high density lipoprotein cholesterol, and serum uric acid were independent determinants of soluble endoglin. Adding tests of ASCVD and endoglin together, in parallel, will increase the sensitivity and decrease specificity in recognizing carotid subclinical atherosclerosis. Evaluating the added value of endoglin to the ASCVD risk model showed significantly improved discrimination with analysis of C-statistics, continuous net reclassification index and integrated discrimination index. Both ASCVD risk and soluble endoglin showed positively linear correlation with carotid intima-media thickness (cIMT) (ß=0.006, P<0.001; ß=0.485, P<0.001). Even with adjustment for other factors, the relationship between log-transformed soluble endoglin with cIMT was still significant (ß=0.369, P<0.001). CONCLUSIONS: The combination of ASCVD risk and endoglin levels increases carotid atherosclerosis recognition.

11.
Med Sci Monit ; 25: 4137-4148, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31158122

RESUMO

BACKGROUND Resveratrol has been shown to possess beneficial activities including antioxidant, anti-inflammatory, and cardioprotective effects through activating a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase family member sirtuin-1 (SIRT1) protein. The current study was undertaken to investigate the role of sirtuin family members (SIRT1-SIRT7) on the anti-inflammation activities of resveratrol in endothelial cells. MATERIAL AND METHODS Primary human umbilical vein endothelial cells (HUVECs) were pretreated with resveratrol before tumor necrosis factor (TNF)-alpha (10-20 µg/L) stimulation. Cell viability was measured using the Cell Counting Kit-8 method. Total RNA was extracted after different treatments and the NimbleGen Human 12×135K Gene Expression Array was applied to screen and analyze SIRTs expression. Quantitative real-time polymerase chain reaction and western blot were applied to verify the results of the gene expression microarrays. Reactive oxygen species (ROS) production was examined using flow cytometry analysis. RESULTS Microarray analysis showed that the expressions of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 showed the tendency to increase while SIRT4 showed the tendency to decrease. SIRT1, SIRT2, SIRT5, and SIRT7 gene expression could be upregulated by pretreatment with resveratrol compared with TNF-alpha alone while there were no obvious differences of SIRT3, SIRT4, and SIRT6 expressions observed in TNF-alpha alone treated cells and resveratrol-TNF-alpha co-treated cells. Interestingly, SIRT1, SIRT2, SIRT3, SIRT4, and SIRT5 siRNA could reverse the effect of resveratrol on ROS production; SIRT1 and SIRT5 siRNA could significantly increase CD40 expression inhibited by resveratrol in TNF-a treated cells. CONCLUSIONS Our results suggest that resveratrol inhibiting oxidative stress production is associated with SIRT1, SIRT2, SIRT3, SIRT4, and SIRT5 pathways; attenuating CD40 expression was only associated with SIRT1 and SIRT5 pathways in TNF-alpha-induced endothelial cells injury.


Assuntos
Resveratrol/farmacologia , Sirtuínas/metabolismo , Sirtuínas/farmacologia , Antioxidantes , Células Cultivadas , China , Expressão Gênica , Regulação da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuínas/genética , Fator de Necrose Tumoral alfa/metabolismo
12.
BMC Nephrol ; 20(1): 201, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159763

RESUMO

BACKGROUND: A low FT3 level is significantly associated with a variety of kidney disease and acute myocardial infarction (AMI). However, it remains unclear whether low FT3 is associated with CI-AKI in patients who underwent pPCI. METHODS: Single-center retrospective study evaluated 363 STEMI patients undergoing pPCI. Patients were classfied into 2 groups, low FT3 group (FT3 < 3.1 pmol/L) and normal FT3 group (FT3 ≥ 3.1 pmol/L);CI-AKI was defined as an increase in the serum creatinine levels of ≥50% or 0.3 mg/dL above the baseline level within 48 h after contrast medium exposure. RESULTS: Overall, 80(22.0%) patients had low FT3, and 59(16.3%) patients developed CI-AKI. The incidence of CI-AKI and in-hospital mortality was significantly higher in patients with low FT3 than normal (31.3% vs 12.0%; 15.0% vs 3.2%, respectively, both p < 0.0001). Multivariate logistic regression analysis indicated that low FT3 was an independent predictor of CI-AKI (odds ratio [OR] = 2.62, 95%CI:1.35-5.07, p < 0.05). In addition, low FT3 was associated with an increased risk of all-cause mortality during a mean follow-up period of 20 months (hazard ratio [HR] = 2.54, 95%CI:1.15-5.60, p < 0.05). CONCLUSION: Low FT3 was associated with CI-AKI, short- and long-term mortality in STEMI patients after pPCI.

13.
Nanotechnology ; 30(35): 355601, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31100742

RESUMO

The inherent susceptibility to oxidation and poor sinterability significantly limit the practical application of Cu-based conductive inks. Most methodologies employed for the inks like organic polymer coatings and inorganic metal deposition are generally ineffective. Herein, we report the design of a novel hierarchical Cu architecture to simultaneously improve the antioxidative and sinterability via a self-passivation mechanism and loose interior structures. The hierarchical Cu architecture was prepared using copper hydroxide, L-ascorbic acid, and polyvinylpyrrolidone in aqueous solution; 40 g Cu were prepared in a scale-up experiment. A possible growth mechanism is proposed, involving the Cu2O-templated and mediated nucleation and growth of Cu nanocrystals, followed by the PVP-directed electrostatic self-assembly of Cu nanocrystals. The synthesized Cu shows high oxidation resistance after stored in ambient environment for 90 d by self-passivation, wherein the dense oxidized external layer prevented further oxidation of Cu, unlike other antioxidative strategies. In addition, the structure became 2D flake after a simple ball-milling for 10 min of 2000r, thus forming a good conductive network at the temperature of 180 °C. Importantly, no obvious decline in the electrical performance after severe surface oxidation. Although the structure cannot offer excellent conductive performance, but it proposes a new solution for the balance of antioxidative capabilities and good sinterability in Cu nanomaterials, thus facilitating greater utilization of Cu-based conductive inks for emerging flexible electronic applications.

14.
Horm Metab Res ; 51(6): 367-374, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30974472

RESUMO

An elevated serum uric acid (SUA) level is closely associated with increased arterial stiffness. However, whether this association is independent of conventional cardiovascular risk factors is controversial. This study aimed to investigate whether SUA is independently associated with arterial stiffness as assessed by Brachial-ankle pulse wave velocity (baPWV), and to what extent this association is dependent on cardiovascular risk factors. Increased arterial stiffness was defined as baPWV>1 400 cm/s. Cardiovascular risk factors were defined as hypertension, diabetes, dyslipidaemia, and a BMI≥24.0 kg/m2. A total of 3 342 subjects (1 334 men and 2008 women, mean age 53.79±13.18 years) were included. SUA levels exhibited a graded elevation with an increasing number of cardiovascular risk factors. In female subjects with more than two cardiovascular risk factors, compared with the first quartile of SUA, higher SUA quartiles were associated with a higher probability of increased baPWV (OR=1.500, 1.478, 1.774 for SUA Q2-Q4). In further stratified association analysis, compared with Q1, SUA quartiles showed a graded association with increased baPWV in subjects with TC≥5.2 mmol/l (OR=1.758, 1.942, 2.354 for Q2, Q3, and Q4 respectively), LDL-C≥3.3 mmol/l (OR=1.510, 2.255 for Q3 and Q4) and FBG≥7.0 mmol/l (OR=1.516, 1.748 for Q3 and Q4). In the Chinese coastal female population, the association of high SUA and increased arterial stiffness is dependent on the coexistence of at least one cardiovascular risk factor, especially hypercholesterolemia.


Assuntos
Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Hipercolesterolemia/complicações , Análise de Onda de Pulso , Ácido Úrico/sangue , Rigidez Vascular , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , China/epidemiologia , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores Sexuais
15.
ACS Appl Mater Interfaces ; 11(8): 8382-8390, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30726050

RESUMO

Elliptic Cu-Ag nanoflakes were syntheszied via facile in situ galvanic replacement between prepared Cu particles and Ag ions. Alloy nanoflakes with high purity and uniformity present a size of 700 × 500 nm, with a thinness of 30 nm. Nontoxic and low-cost polyvinyl pyrrolidone was used as a dispersant and structure-directing agent, promoting the formation of the remarkable structure. Synthesized nanoflakes were utilized as a filler for conductive paste in an epoxy resin matrix. Conductive patterns on flexible substrates with a resistivity of 3.75 × 10-5 Ω·cm could be achieved after curing at 150 °C for 2 h. Compared with traditional silver microflakes, smart alloy nanoflakes provide much improved conductive interconnection, whose advantage could be attributed to their nanoscale thicknesses. It is also noteworthy that the conductive patterns are able to tolerate multiple bendings at different angles, having good conductivity even after 200 repeated bendings. Therefore, alloy nanoflakes could be a promising candidate conductive filler for flexible printing electronics, electronic packaging, and other conductive applications.

16.
Anatol J Cardiol ; 21(2): 60-67, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30694798

RESUMO

OBJECTIVE: Low free triiodothyronine (fT3) is common in elderly patients with cardiovascular disease. The purpose of this study was to evaluate the relationship between low fT3 and contrast-induced acute kidney injury (CI-AKI), including the long-term outcomes, in elderly patients after a percutaneous coronary intervention (PCI). METHODS: A total of 350 patients aged ≥75 years who underwent PCI between January 2012 and December 2015 were consecutively enrolled. The perioperative thyroid function, including fT3, was measured before PCI. A low fT3 was defined as fT3<3.1 pmol/L with normal thyrotropin and free thyroxine. CI-AKI was defined as an absolute serum creatinine (SCr) increase ≥0.30 mg/dL or a relative increase in SCr ≥50% from the baseline value within 48 hours after contrast media exposure. A multivariate logistic regression analysis was applied to analyze whether low fT3 was an independent risk factor for CI-AKI. The Cox regression analysis was used to evaluate the relationship between low fT3 and long-term prognosis. RESULTS: A total of 46 (13.1%) patients developed CI-AKI. The incidence of CI-AKI was significantly higher in the low fT3 group than in the normal group (26.5% vs. 9.9%, p<0.01). A multivariable logistic analysis demonstrated that a low fT3 level was significantly related to CI-AKI [odds ratio (OR)=2.41; 95% confidence interval (CI), 1.11-5.27; p=0.027]. The Cox regression analysis showed that a low fT3 was associated with long-term mortality [adjusted hazard ratio (HR)=2.00; 95% CI, 1.04-3.83; p=0.037] during the follow-up of mean 1.67 years. CONCLUSION: A low fT3 concentration was independently associated with CI-AKI and poor prognosis in elderly patients who had undergone PCI.


Assuntos
Lesão Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Tri-Iodotironina/sangue , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/mortalidade , Idoso , China , Estudos de Coortes , Feminino , Serviços de Saúde para Idosos , Humanos , Modelos Logísticos , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
17.
J Mol Histol ; 50(2): 91-103, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30604255

RESUMO

LPS-induced septic cardiomyopathy has been found to be connected with mitochondrial stress through unknown mechanisms. Mitochondrial fission is an early event in mitochondrial dysfunction. The aim of our study was to determine the role and regulatory mechanism of mitochondrial fission in the progression of LPS-induced septic cardiomyopathy, with a particular focus on Mst1 and F-actin. Our data demonstrated that Mst1 expression was rapidly upregulated in LPS-treated hearts and that increased Mst1 promoted cardiomyocyte death by inducing mitochondrial stress. Mechanistically, elevated expression of Mst1 upregulated Drp1, and the latter initiated mitochondrial fission. Excessive mitochondrial fission caused mitochondrial oxidative injury, mitochondrial membrane potential reduction, mitochondrial proapoptotic element translocation into the cytoplasm/nucleus, mitochondrial energy dysfunction and mitochondrial apoptosis activation. Inhibition of mitochondrial fission sustained mitochondrial function and favored cardiomyocyte survival. Furthermore, we identified F-actin degradation as an apparent downstream event of mitochondrial fission activation in the context of LPS-induced septic cardiomyopathy. Stabilization of F-actin attenuated fission-mediated cardiomyocyte death. Altogether, our results define the Mst1/Drp1/mitochondrial fission/F-actin axis as a new signaling pathway that mediates LPS-related septic cardiomyopathy by inducing mitochondrial stress and cardiomyocyte death. Therefore, Mst1 expression, mitochondrial fission modification and F-actin stabilization may serve as potential therapeutic targets for sepsis-related myocardial injury.


Assuntos
Cardiomiopatias/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Dinâmica Mitocondrial , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Sepse/complicações , Transdução de Sinais , Actinas/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/microbiologia , Morte Celular , Células Cultivadas , GTP Fosfo-Hidrolases/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/patologia , Sepse/induzido quimicamente , Regulação para Cima
18.
J Cell Mol Med ; 23(4): 3032-3039, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30697920

RESUMO

OBJECTIVE: This study aimed to investigate the effects of transforming growth factor ß1 (TGF ß1) and hepatocyte growth factor (HGF) on the expression of connective tissue growth factor (CTGF) in human atrial fibroblasts, and to explore the relationship of these factors in atrial fibrosis and atrial anatomical remodelling (AAR) of patients with atrial fibrillation (AF). METHODS: Fresh right auricular appendix tissue of 20 patients with rheumatic heart disease undergoing valve replacement surgery was collected during surgeries, 10 patients had sinus rhythm(SR), and 10 patients had chronic atrial fibrillation (CAF). Atrial fibroblasts were then cultured from the tissues with differential attachment technique and treated with either TGFß1 (10 ng/mL) or HGF (100 ng/mL). CTGF mRNA levels were measured by RT-PCR, and CTGF protein content was determined using immunofluorescence and Western blotting assays. RESULTS: CAF group had higher left atrial diameters (LADs) and higher CTGF mRNA expression in atrial fibroblasts compared with SR group. The CTGF protein content in CAF group was higher than that of SR group and positively correlated with LAD and AF duration. After CAF group was treated with TGFß1, CTGF mRNA and protein expression were significantly down-regulated, whereas when treated with HGF, expression was up-regulated compared with SR group. CONCLUSIONS: Increased CTGF expression was associated with enlarged LAD, atrial fibrosis and AAR in patients with AF. TGFß1 and HGF regulate CTGF expression in human atrial fibroblasts with up-regulation of mRNA and down-regulation of protein, therefore, either promote or inhibit atrial fibrosis, which could be related to the incidence and persistence of AF.

19.
Front Physiol ; 9: 1447, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30450052

RESUMO

Aim: We investigated the underlying mechanisms in atrial fibrillation (AF) associated with R33Q mutation and Ca2+-triggered activity. Methods and Results: We examined AF susceptibility with intraesophageal burst pacing in the sarcoplasmic reticulum (SR) Ca2+ leak model calsequestrin 2 R33Q (Casq2R33Q/R33Q) mice. Atrial trigger appeared in R33Q mice but not WT mice (17.24%, 5/29 vs. 0.00%, 0/32, P < 0.05). AF was induced by 25 Hz pacing in R33Q mice (48.27%, 14/29 vs. 6.25%, 2/32, P < 0.01). The mice were given 1.5 mg/kg isoproterenol (Iso), and the incidences of AF increased (65.51%, 19/29 vs. 9.21%, 3/32, P < 0.01). Electrophysiology experiments and the recording of intracellular Ca2+ indicated significant increases in the Ca2+ sparks (5.24 ± 0.75 100 µM-1.s-1 vs. 0.29 ± 0.04 100 µM-1.s-1, n = 20, P < 0.05), intracellular free Ca2+ (0.238 ± 0.009 µM vs. 0.172 ± 0.006 µM, n = 20, P < 0.05), Ca2+ wave (11.74% vs. 2.24%, n = 20, P < 0.05), transient inward current (ITi) (-0.56 ± 0.02 pA/pF vs. -0.42 ± 0.01 pA/pF, n = 10, P < 0.05), and oscillation in membrane potentials (10.71%, 3/28 vs. 4.16%, 1/24, P < 0.05) in the R33Q group, but there was no significant difference in the L-type calcium current. These effects were enhanced by Iso, and the inhibition of calmodulin-dependent protein kinase II (CaMKII) by 1 µM KN93 reversed the effects of Iso on Ca2+ sparks (5.01 ± 0.66 100 µm-1.s-1 vs. 11.33 ± 1.63 100 µm-1.s-1, P < 0.05), intracellular Ca2+ (0.245 ± 0.005 µM vs. 0.324 ± 0.008 µM, P < 0.05), Ca2+ wave (12.35% vs. 17.83%, P < 0.05), ITi (-0.61 ± 0.02 pA/pF vs. -0.78 ± 0.03 pA/pF, n = 10, P < 0.05), and oscillation in membrane potential (17.85% 5/28 vs. 32.17% 9/28, P < 0.05). The reduction of ryanodine receptor 2 (RyR2) stable subunits (Casq2, triadin, and junctin) rather than RYR2 and the increase in CaMKII, phosphor-CaMKII, phosphor-RyR2 (Ser 2814), SERCA, and NCX1.1 was reflected in the R33Q group. Conclusion: This study demonstrates that the increase in spontaneous calcium elevations corresponding to ITi that may trigger the oscillation in membrane potentials in the R33Q group, thereby increasing the risk of AF. The occurrence of spontaneous calcium elevations in R33Q atrial myocytes is due to the dysfunction of RyR2 stable subunits, CaMKII hyperactivity, and CaMKII-mediated RyR phosphorylation. An effective therapeutic strategy to intervene in Ca2+-induced AF associated with the R33Q mutation may be through CaMKII inhibition.

20.
ACS Appl Mater Interfaces ; 10(44): 38493-38505, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30351905

RESUMO

Graphene and silver nanowires (AgNWs) are ideal fillers for conductive polymer composites, but they tend to aggregate in the polymer matrix due to the lack of surface functional groups and large specific surface area, which is hard for the polymer composites filled with them to reach their full potential. Here, ternary hybrids with multidimensional architectures including 3D polystyrene (PS) microspheres, 2D reduced graphene oxide (RGO) nanosheets, and 1D AgNWs are obtained using a simple, but effective, electrostatic attraction strategy. The electrical conductivity (136.25 S m-1) of the ternary hybrid conductive nanocomposites filled with RGO and AgNWs is significantly higher than that of the nanocomposites containing only RGO (3.255 S m-1) at the same total filler loading due to the synergistic effect of RGO and AgNWs. The conductive nanocomposites simultaneously present a low percolation threshold of 0.159 vol % and a maximum electrical conductivity of 1230 S m-1 at 3.226 vol % filler loading. Moreover, a flexible electronic skin based on the multidimensional ternary hybrids is presented, and it exhibits large stretchability, high gauge factor, and excellent cyclic working durability, which is successfully demonstrated in monitoring prosthetic finger motions.


Assuntos
Nanocompostos/química , Nanofios/química , Polímeros/química , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Grafite/química , Humanos , Microesferas , Óxidos/química , Poliestirenos/química , Prata/química
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